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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-10-6
pubmed:abstractText
We compared the biological effects of the CXC chemokine SDF-1alpha on immunomagnetically purified CD34+ cells isolated from human normal bone marrow (NBM), leukapheresis products (LP) and patients with chronic myeloid leukaemia (CML). LP CD34+ cells showed a significantly stronger migration response to SDF-1alpha (100 ng/ml) than CD34+ cells isolated from the peripheral blood (PB) of CML patients (P < 0.05). The chemotactic response to SDF-1alpha was also reduced in CML BM CD34+ cells in comparison to NBM CD34+ cells but the observed differences were not statistically significant. In analogy to normal CD34+ cells circulating CML PB CD34+ cells were less responsive to SDF-1alpha than their BM counterparts (P < 0.05). Furthermore, SDF-1alpha elicited similar concentration-dependent growth suppressive effects on normal and CML CD34+ cells (P > 0.05) in colony-forming cell assays. We then demonstrated that SDF-1alpha triggers intracellular calcium increases in CD34+ cells and there were no differences in the time course and dose response characteristics of normal and CML CD34+ cells. The reduced migration response to SDF-1alpha in CML CD34+ cells was not due to a down-regulation of the SDF-1alpha receptor CXCR-4 as flow cytometric analysis revealed similar CXCR-4 expression levels on NBM, LP, CML PB and CML BM CD34+ cells (P > 0.05). Finally, no differences in the modulation of CXCR-4 levels in response to SDF-1alpha and serum were observed in CML and normal CD34+ cells. Our data suggest that the impaired chemotactic response of CML CD34+ cells to SDF-1alpha is not caused by a lack or complete uncoupling of CXCR-4, but may be due to an intracellular signalling defect downstream of the receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1652-60
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10995013-Antigens, CD19, pubmed-meshheading:10995013-Antigens, CD34, pubmed-meshheading:10995013-B-Lymphocytes, pubmed-meshheading:10995013-Calcium, pubmed-meshheading:10995013-Cell Movement, pubmed-meshheading:10995013-Chemokine CXCL12, pubmed-meshheading:10995013-Chemokines, CXC, pubmed-meshheading:10995013-Chemotactic Factors, pubmed-meshheading:10995013-Fusion Proteins, bcr-abl, pubmed-meshheading:10995013-Hematopoietic Stem Cells, pubmed-meshheading:10995013-Humans, pubmed-meshheading:10995013-Leukapheresis, pubmed-meshheading:10995013-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:10995013-Neprilysin, pubmed-meshheading:10995013-Receptors, CXCR4, pubmed-meshheading:10995013-Stem Cells, pubmed-meshheading:10995013-Tumor Stem Cell Assay, pubmed-meshheading:10995013-Up-Regulation
pubmed:year
2000
pubmed:articleTitle
Biological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells.
pubmed:affiliation
Department of Haematology, University Hospital Essen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't